The objectives of these studies are to elucidate the role of brain monoamines in the regulation of luteinizing hormone (LH) and prolactin secretion, and to utilize this information for the pharmacological control of mammary tumors. We previously demonstrated that complete deafferentation of the medial basal hypothalamus caused a total disappearance of norepinephrine without affecting the dopamine content within the island. Treatment of complete-deafferented rats with alpha- methyl-p-tyrosine (alpha-MPT) stimulates prolactin release. The endogenous dopamine pool will be labeled with intraventricularly administered H3-tyrosine. Changes in the metabolism of dopamine- containing neurons isolated within the deafferented island will be directly correlated with the alpha-MPT induced changes in prolactin secretion. Serum and pituitary LH and prolactin levels will be measured using the NIAMD rat radioimmunoassays. The post-ovariectomy rise in LH is only partially blocked by complete deafferentation. Estrogen and progesterone will be administered to these animals in order to study the site of negative feedback of LH secretion. The role of dopaminergic neurons in steroid feedback will be determined using pharmacological agents which potentiate, or inhibit dopamine synthesis, respectively DOPA and alpha-MPT. Direct electrical stimulation of the deafferented MBH will be performed to stimulate or inhibit LH and prolactin release. The role of dopaminergic neurons in these responses will be pharmacologically tested. Electron microscopic studies will be performed to eliminate the possibility of the regeneration of severed neurons following deafferentation. Information from these studies will be utilized to develop techniques to pharmacologically control the growth of mammary tumors induced by 7, 12 dimethylbenzantracene.